Efeito tripanocida de peptídeos derivados das dinoponeratoxinas

Abstract

Chagas disease is an important public health problem and benznidazole, the only drug used in treatment, has limited efficacy and causes serious adverse effects. In this context, it is necessary to search for therapeutic strategies that promote greater selectivity for the parasite, reducing the complications caused in the host. The venom of the giant ant Dinoponera quadriceps is rich in peptides, called dinoponeratoxins (DnTxs), whose effects make then similar to antimicrobial peptides. Dntx Dq-2561, in a recent study, showed a better antichagasic effect, with a high selectivity index (IS) (80,3), being considered the most promising, however, it was shown to be hemolytic. So, two fragments of the DnTx Dq-2561 were designed and synthesized: Dq-2561[1- 15] and Dq-2561[3-15]. The objective of the present work was to evaluate the trypanocidal potential of peptides derived from DnTx Dq-2561 on the evolutionary forms of Trypanosoma cruzi strain Y (benznidazole resistant strain). The toxicity of Dq- 2561[1-15] and Dq-2561[3-15] peptides was evaluated in LLC-MK2 host cells, by the MTT reduction method. The trypanocidal effect was evaluated on epimastigotes (cultured in LIT medium, at 28ºC), trypomastigotes and amastigotes (obtained through infection of LLC-MK2 cells and cultured in DMEM medium, at 37ºC and 5% CO2), being determined the IS. All tests were performed in triplicate and the average results from three independent experiments were used for statistical analysis, where the results were compared using the one-way ANOVA test, with Bonferroni's post-test. The peptides derived from DnTx Dq-2561 showed an effect against the epimastigote and trypomastigote forms of T. cruzi strain Y, presenting less toxicity in LLC-MK2 host cells. However, Dq-2561[1-15] demonstrated an effect more similar to the parental peptide, with a high selectivity index (72.9) and antiamastigote effect. Therefore, the smaller size of these peptides brings new perspectives for the emergence of new therapeutic alternatives for Chagas' disease.